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Nikhil S. Malvankar

Associate Professor of Molecular Biophysics and Biochemistry

Contact Information

Nikhil S. Malvankar

Mailing Address

  • Yale Microbial Sciences Institute

    Malvankar lab, Advance Biosciences Center (ABC), 300 Heffernan Drive

    West Haven, CT 06516

    United States

Protein Nanowires Lab
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Research Summary

Single-cell Imaging and Control of Microbial Functions using Protein Nanowires “Life is nothing but an electron looking for a place to rest.” - Nobel Laureate A. Szent-Gyorgi

Electron transfer is central to all life processes. To avoid damage, organisms have evolved strategies to eliminate the surplus of electrons created by metabolism, using oxygen-like electron acceptors, which act as electron sinks. However, microbes that live in areas with no oxygen, such as those that reside in the deep ocean, in soil, or in the human body, have evolved strategies to export electrons to extracellular acceptors, such as minerals and other bacteria. Geobacter uses long, thin, conductive filaments called “nanowires” to export electrons. Nanowires are fundamental to the global environment & are also required in some infections.

Geobacter nanowires have intrigued the scientific community since they were first identified in 2002. Until recently, nanowires were thought to be pili. However, our lab’s recent work demonstrates that pili structure is inconsistent with electron transfer, whereas cytochrome filaments could transfer electrons through a continuous chain of heme groups. We are now testing hypotheses that (i) these cytochromes are the nanowires (Cell 2019, Nature Chem.Bio. 2020, Nature Micro.­ 2023), and that (ii) pili function akin to a piston to secrete cytochrome across the outer membrane (Nature 2021). We aim to determine nanowires' structure, assembly, and electron transfer mechanism and evaluate their role in respiration, communication, and pathogenesis.

Extensive Research Description

By combining experimental and computations, we are addressing three key questions:

  1. How do microbes build & use nanowires?
  2. How are electrons transferred from the bacterial cytoplasm to surface-displayed nanowires?
  3. Can nanowire conductivity be tuned via light, pressure, electric- & magnetic-fields to control bacteria?

Using what we learn from these studies, our long-term vision is to monitor and control the growth of microbes residing in the deep ocean, in soil, or in the human body to use nanowires in four areas:

1) Fundamental studies to elucidate how diverse microbes assemble and use various nanowires.

2) Repair soil and marine environmental health using microbial nanowire-mediated electron exchange.

3) Restore rhizosphere health by targeting nanowire-mediated microbe-plant interactions; and

4) Restore human health by controlling the growth and colonization of clinically important microbes.

Towards this vision, in the shorter term (next 3-5 years), we plan to make inroads in the:

1) In situ structural and functional imaging of metabolism within microbial communities using our electron imaging (Nature Nano.) combined with cryo-electron microscopy & tomography (with Jun Liu)

2) Understanding conductivity mechanisms employed by protein nanowires. We are determining how nanowires move electrons, ions, spins, and excitons at unprecedented ultrafast (< 200 fs) rates ( Nature Comm. 2022) and over centimeter distances. We have found a novel electron escape route in proteins to avoid oxidative damage (PNAS 2021) and how cooling speeds up electrons (Science Adv. 2022).

3) Control bacterial metabolism to develop Antibiotics: Disrupting electron export to inhibit growth and adhesion of pathogens and Probiotics: Accelerating electron export to promote growth of commensals.

Small wires, big opportunities. Protein nanowires provide unprecedented ability to control microbial function and design custom microbial communities. We are establishing a fundamentally new class of electron-conducting protein nanowires and electrogenetics, making it possible to electronically control any microbe as electronic analogs of GFP and optogenetics to monitor and control the growth, communication, and colonization of microbes deep inside the Earth and in human cells.

Projects involve structural studies, genetically engineering nanowire conductivity, nanoscale electron transfer measurements in nanowires and living biofilms, spectroelectrochemistry, and building and experimentally testing computational models through ongoing collaborations with Batista and Brudvig (Yale, Chem.), Lisa Craig (Canada), Olivera Francetic (France), and Carlos Salgueiro (Portugal).

We have several interdisciplinary projects embedded in these larger goals that would be great rotation projects. They provide training in a variety of biophysical, molecular biology, and biochemical techniques and are likely to yield positive results/publications within the rotation. Please chat to match your interests with training opportunities. Projects are experimentally or computationally-oriented, with possibilities of combining both. No prior background is necessary.

Please chat with PI or one of laboratory members to match your interests with our training opportunities. Rotation projects are experimentally or computationally-oriented with the possibility of combining both, and no prior background in a specific discipline is necessary.

Join our lab meetings in person or via Zoom on Wednesday at 11 AM (with international collaborators) and 12:30 PM (group). We can adapt our lab meeting schedule to accommodate your class schedule.


Coauthors

Research Interests

Bacteria, Anaerobic; Bacterial Adhesion; Bacterial Infections; Biophysics; Chemistry, Physical; Electron Transport; Environmental Microbiology; Microscopy, Atomic Force; Nanotechnology

Public Health Interests

Environmental Health; Infectious Diseases; Respiratory Disease/Infections

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Selected Publications

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